Abstract
BackgroundSchistosomiasis is one of the most common parasitic diseases affecting millions of humans and animals worldwide. Understanding the signal transduction pathways and the molecular basis of reproductive regulation in schistosomes is critically important for developing new strategies for preventing and treating these infections. Syk kinases regulate the proliferation, differentiation, morphogenesis, and survival of various types of cells and have been identified in invertebrates. Tyrosine kinase 4 (TK4), a member of the Syk kinase family, plays a pivotal role in gametogenesis in S. mansoni, affecting the development of the testis and ovaries in this parasite. The role of TK4, however, in the reproduction of S. japonicum is poorly understood.MethodsHere, the complete coding sequence of TK4 gene in S. japonicum (SjTK4) was cloned and characterized. The expression of SjTK4 was analyzed at different life-cycle stages and in various tissues of S. japonicum by qPCR. Piceatannol, a Syk kinase inhibitor, was applied to S. japonicum in vitro. The piceatannol-induced morphological changes of the parasites were observed using confocal laser scanning microscopy and the alterations in important egg-shell synthesis-related genes were examined using qPCR analyses.ResultsSjTK4 mRNA was differentially expressed throughout the life-cycle of S. japonicum. SjTK4 mRNA was highly expressed in the ovary and testis of S. japonicum, with the level of gene expression significantly higher in males than in females. The expression levels of some important egg-shell synthesis related genes were higher in the piceatannol-treated groups than in the vehicle-treated control group and the number of eggs and germ cells also decreased in a concentration-dependent manner. Importantly, large pore-like structures can be found in the testis and ovaries of males and females after treating with piceatannol.ConclusionThe results suggest that SjTK4 may play an important role in regulating gametogenesis of S. japonicum. The findings may help better understand the fundamental biology of S. japonicum. Moreover, the effect of S. japonicum treatment by piceatannol provides us with a new idea that inhibition of SjTK4 signaling pathway can effectively retard the development of the testis and ovaries.
Highlights
Schistosomiasis is one of the most common parasitic diseases affecting millions of humans and animals worldwide
Using multiple sequence alignment of the amino acid sequences, we found that SjTK4 contains two Src homology 2 (SH2) domains and one TK domain
spleen tyrosine kinase (Syk)-TKs represent a distinct group of cellular TKs in addition to belonging to the large group of Src-like TKs, with the main difference being that Syk-TKs possess two SH2 domains, whereas Src-family members have one SH2 and one SH3 domain [12]
Summary
Schistosomiasis is one of the most common parasitic diseases affecting millions of humans and animals worldwide. Understanding the signal transduction pathways and the molecular basis of reproductive regulation in schistosomes is critically important for developing new strategies for preventing and treating these infections. After S. japonicum infects a definitive host, the female’s reproductive system matures to produce eggs subsequent to the pairing between male and female worms. Understanding the significance of the development and fundamental regulations in the reproductive biology of schistosomes, as well as in the pathogenic consequences of schistosomiasis, is still in its initial stage. Understanding the signal transduction pathways and the molecular basis of reproductive regulation in schistosomes is critically important for developing new strategies for preventing and treating schistosomiasis. A better understanding of the fundamental biology of flatworms is of broad scientific interest
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